The goal of the University of Washington (UW) Alzheimer's Disease Research Center (ADRC) is to continue to support and enhance ongoing research projects and new research initiatives addressing the etiology, pathogenesis, and treatment of Alzheimer's disease (AD) and related disorders. An interdisciplinary collaborative team of basic and clinical investigators, health care professionals and administrative personnel has coalesced at the UW to support and carry out an array of productive AD research programs. These have included research projects addressing the genetics, molecular neurobiology and neuroendocrinology of AD and normal aging, as well as research projects addressing the epidemiology of AD and normal aging, as well as research projects addressing the epidemiology of AD and both the behavioral and pharmacologic treatments of AD. Such projects have been supported within the ADRC, in the greater UW research community and nationally through direct collaborations and formal multi-center programs such as CERAD and the fellows and junior faculty can acquire research skills and experience working in an interdisciplinary AD research setting. ADRC faculty have competed successfully for fellowship and junior faculty career development programs to support such individuals, and have placed special emphasis on career development of women and minorities in AD research. Accomplishments of the previous funding period have covered a broad spectrum of basic, clinical and behavioral contributions to knowledge about AD. Accomplishments of the previous funding period have covered a broad spectrum of ADRC investigators to discover mutations causing early onset familial AD and frontotemporal dementia, to the successful efforts of ADRC investigators to lead to completion a multi-center cooperative clinical trial (with the ADCS) evaluating efficacy of pharmacologic and behavioral treatment approaches to disruptive agitation in AD. The current application requests continuation of all ADRC cores and proposes four research projects. Two ongoing projects continue productive programs addressing the genetics of AD and addressing the role of estrogen in neuroprotection. A new clinical neuroendocrinology project addresses insulin and cortisol interactions in AD. A new molecular neurobiology project addresses modulation of A- beta production.